Differential Gene Expression Profiles of Cells from Normal, Traumatic and Idiopathic Scoliotic Discs Identify Molecular Dysregulation in Scoliosis
Notice bibliographique
Résumé
Introduction The etiology of the spinal deformity in idiopathic scoliosis is unclear to date, both with respect to initiation and progression of the disease. While the influence of certain genetic factors has been established, the role of the intervertebral disc (IVD) in the development of idiopathic scoliosis has scarcely been investigated. The aim of this study was to identify molecular differences between disc cells from patients with idiopathic scoliosis in comparison with trauma patients and healthy individuals. To address this aim, cellular gene expression profiles were analyzed by microarray and quantitative RT-PCR. Material and Methods Surgical samples from IVDs of patients with idiopathic scoliosis were obtained after informed consent and approval of the local ethical commission at the time of discectomy during spinal fusion surgery. The disorder and exact curve pattern were documented for further records. Control disc samples were obtained from trauma fusion cases and from organ donors with no known disc disorders according to local and institutional ethical guidelines. Annulus fibrosus (AF) and nucleus pulposus (NP) tissues were separated and cells were isolated by enzymatic digestion within 24 hours. Total RNA was extracted from the cells and subjected to Affymetrix GeneChip® expression profiling. Genes with significant differences between scoliotic and control samples were further analyzed using real time RT-PCR. Results After exclusion of RNA samples with insufficient quality or quantity, the following numbers of samples were used for microarray profiling: 10 AF and 6 NP samples from scoliotic discs; 5 AF and 4 NP samples from traumatic discs; 4 AF and 4 NP samples from healthy discs of organ donors. Microarray data revealed that 52 genes were more highly expressed in scoliotic vs. healthy AF and 26 genes in scoliotic vs. traumatic AF, whereby 21 genes showed higher expression in scoliotic AF compared with both control groups. In addition, 116 genes were more highly expressed in scoliotic vs. healthy NP, 45 genes in scoliotic vs. traumatic NP, and 40 of those in scoliotic NP compared with both control groups. Quantitative gene expression analysis by real time RT-PCR ( n = 6 per group) confirmed significantly increased mRNA levels of S100A8, S100A12, MMP8, MMP13 and Collagen X in annulus fibrosus cells from scoliotic discs ( p < 0.05; Kruskal-Wallis test of log2 transformed data). Conclusion Results of this study reveal significant changes in the gene expression profile of IVD cells from patients with idiopathic scoliosis compared with patients with traumatic disc damage or donors with no known disc disorders. MMP8 and MMP13 are important collagenases involved in disc matrix degradation; while elevated S100 calcium binding proteins may indicate an inflammatory reaction. Interestingly, MMP13 has also been up-regulated by imbalanced loading in an IVD organ culture model. Better knowledge of the dysregulation of structural or regulatory molecules may identify underlying mechanisms of spinal deformities, which will help defining new targets for early therapeutic intervention. Acknowledgment This study is supported by AOSpine International.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».